Injectable and inhalable formulations

Abstract

The present invention relates to aqueous pharmaceutical formulations, methods for their production, and uses thereof. The aqueous pharmaceutical formulations comprise a salt of an optionally substituted dimethyltryptamine compound and water, with a pH from 5 to 6.5, preferably from about 5 to about 6, and a concentration of the optionally substituted dimethyltryptamine compound of about 10 mg/ml or greater as the freebase equivalent. These formulations can comprise an effective dose of an optionally substituted dimethyltryptamine compound for use in psychedelic assisted therapy within a volume of 5 ml or less. Such formulations are surprisingly suitable both for intramuscular injection and nebulised inhalation, being both stable and clinically acceptable, and have potential uses in the treatment of psychiatric or neurological disorders.

The invention claimed is: 
     
       1. A pharmaceutical formulation suitable for intramuscular injection, comprising a salt of a compound of Formula IB: 
       
         
           
           
               
               
           
         
         wherein: 
         n is 0; 
         R 1b  is independently selected from —R 4b , —OH, —OR 4b , —O(CO)R 4b , monohydrogen phosphate, —F, —Cl, —Br or —I; 
         R 2b  is C( xb H) 3 ; 
         R 3b  is C( xb H) 3 ; 
         each R 4b  is independently selected from C 1 -C 4 alkyl; and 
         each  xb H,  yb H and  z H is independently selected from protium or deuterium; 
       
       and a Brønsted acid having a pKa of from about 3 to about 5; 
       a base agent, water, and optionally a buffer which is separate to the salt; 
       wherein the formulation has a pH of from about 5 to about 6.5, a concentration of the compound of Formula IB of about 10 mg/ml or greater as the freebase equivalent, and an osmolality of from about 250 to about 350 mOsm/Kg; and 
       wherein the formulation comprises a dose of the compound of Formula IB within a volume of 5 ml or less. 
     
     
       2. The formulation of  claim 1 , wherein the formulation has a pH of from about 5 to about 6. 
     
     
       3. The formulation of  claim 1 , wherein the formulation comprises a dose of the compound of Formula IB within a volume of 3 ml or less. 
     
     
       4. The formulation of  claim 1 , wherein R 2b  is CD 3  and R 3b  is CD 3 ; and/or wherein each  yb H is D. 
     
     
       5. The formulation of  claim 1 , wherein the compound of Formula IB is N,N-dimethyltryptamine. 
     
     
       6. The formulation of  claim 1 , wherein the compound of Formula IB is selected from the group consisting of α,α-dideutero-N,N-dimethyltryptamine, α,α-dideutero-N,N-di(trideuteromethyl)tryptamine, α,α,β,β-tetradeutero-N,N-dimethyltryptamine, and α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine. 
     
     
       7. The formulation of  claim 1 , wherein the Brønsted acid is selected from the group consisting of fumaric acid, tartaric acid, citric acid, acetic acid, lactic acid and gluconic acid. 
     
     
       8. The formulation of  claim 1 , wherein the concentration of the compound of Formula IB is from about 20 mg/mL to about 40 mg/mL (as the freebase equivalent). 
     
     
       9. The formulation of  claim 1 , wherein the formulation comprises the buffer which is separate to the salt, optionally wherein the buffer comprises an acetate salt and acetic acid; or a citrate salt and citric acid; or a phosphate salt and phosphoric acid; or the buffer comprises an acetate salt, a citrate salt, or a phosphate salt. 
     
     
       10. The formulation of  claim 1 , wherein the formulation further comprises a tonicity agent and/or a pH adjuster. 
     
     
       11. The formulation of  claim 1 , wherein the formulation consists of the salt of the compound of Formula IB, water, the base agent and optionally the buffer and/or a tonicity agent and/or pH adjuster. 
     
     
       12. The formulation of  claim 1 , having an oxygen content of less than 5 ppm, or less than 2 ppm. 
     
     
       13. The formulation of  claim 1 , comprising the salt of the compound of Formula IB, the base agent, water, the buffer which is separate to the salt, and a tonicity agent or pH adjuster. 
     
     
       14. The formulation of  claim 13 , comprising a salt of the compound of Formula IB; the base agent which is selected from potassium hydroxide or sodium hydroxide; water; the buffer which is a citrate salt; and the tonicity agent or pH adjuster which is an acid. 
     
     
       15. A kit suitable for preparing the formulation of  claim 1 , said kit comprising the salt of the compound of Formula IB; optionally a tonicity agent and/or a pH adjuster; the base agent and optionally the buffer which is separate to the salt. 
     
     
       16. A lyophilised powder formulation comprising the formulation according to  claim 1  which has been lyophilised. 
     
     
       17. The formulation of  claim 1 , wherein the concentration of the compound of Formula IB is about 25 mg/mL (as the freebase equivalent). 
     
     
       18. The formulation of  claim 1 , wherein the compound of Formula IB is a deuterated N,N-dimethyltryptamine. 
     
     
       19. The formulation of  claim 18 , wherein the deuterated N,N-dimethyltryptamine is selected from the group consisting of α,α-dideutero-N,N-dimethyltryptamine, α,α-dideutero-N,N-di(trideuteromethyl)tryptamine, α,α,β,β-tetradeutero-N,N-dimethyltryptamine, and α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine. 
     
     
       20. A pharmaceutical formulation suitable for intramuscular injection, comprising:
 a fumarate salt of deuterated N,N-dimethyltryptamine selected from the group consisting of α,α-dideutero-N,N-dimethyltryptamine, α,α-dideutero-N,N-di(trideuteromethyl)tryptamine, α,α,β,β-tetradeutero-N,N-dimethyltryptamine, and α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine; 
 a base agent selected from potassium hydroxide and sodium hydroxide; 
 water; and 
 a buffer which comprises an acetate salt, a citrate salt, or a phosphate salt; 
 
       wherein the formulation has a pH of from about 5 to about 6.5, a concentration of the deuterated N,N-dimethyltryptamine from about 20 mg/mL to about 40 mg/mL as the freebase equivalent, and an osmolality of from about 250 to about 350 mOsm/Kg; and 
       wherein the formulation comprises a dose of the deuterated N,N-dimethyltryptamine within a volume of 5 ml or less. 
     
     
       21. A formulation according to  claim 20 , comprising a fumarate salt of α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine.